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Biochem Biophys Res Commun. 2014 May 3. pii: S0006-291X(14)00795-5. doi: 10.1016/j.bbrc.2014.04.132. [Epub ahead of print]
The PDZ-binding motif of the avian NS1 protein affects transmission of the 2009 influenza A(H1N1) virus.
Kim JI1, Hwang MW1, Lee I1, Park S1, Lee S1, Bae JY1, Heo J2, Kim D2, Jang SI2, Park MS1, Kwon HJ2, Song JW3, Park MS4.
Author information
Abstract
By nature of their segmented RNA genome, influenza A viruses (IAVs) have the potential to generate variants through a reassortment process. The influenza nonstructural (NS) gene is critical for a virus to counteract the antiviral responses of the host. Therefore, a newly acquired NS segment potentially determines the replication efficiency of the reassortant virus in a range of different hosts. In addition, the C-terminal PDZ-binding motif (PBM) has been suggested as a pathogenic determinant of IAVs. To gauge the pandemic potential from human and avian IAV reassortment, we assessed the replication properties of NS-reassorted viruses in cultured cells and in the lungs of mice and determined their transmissibility in guinea pigs. Compared with the recombinant A/Korea/01/2009 virus (rK09; 2009 pandemic H1N1 strain), the rK09/VN:NS virus, in which the NS gene was adopted from the A/Vietnam/1203/2004 virus (a human isolate of the highly pathogenic avian influenza H5N1 virus strains), exhibited attenuated virulence and reduced transmissibility. However, the rK09/VN:NS-PBM virus, harboring the PBM in the C-terminus of the NS1 protein, recovered the attenuated virulence of the rK09/VN:NS virus. In a guinea pig model, the rK09/VN:NS-PBM virus showed even greater transmission efficiency than the rK/09 virus. These results suggest that the PBM in the NS1 protein may determine viral persistence in the human and avian IAV interface.
Copyright ? 2014. Published by Elsevier Inc.
KEYWORDS:
Influenza A virus, Interferon, NS1 protein, PDZ-binding motif, Transmission
PMID:
24802398
[PubMed - as supplied by publisher]
The PDZ-binding motif of the avian NS1 protein affects transmission of the 2009 influenza A(H1N1) virus.
Kim JI1, Hwang MW1, Lee I1, Park S1, Lee S1, Bae JY1, Heo J2, Kim D2, Jang SI2, Park MS1, Kwon HJ2, Song JW3, Park MS4.
Author information
Abstract
By nature of their segmented RNA genome, influenza A viruses (IAVs) have the potential to generate variants through a reassortment process. The influenza nonstructural (NS) gene is critical for a virus to counteract the antiviral responses of the host. Therefore, a newly acquired NS segment potentially determines the replication efficiency of the reassortant virus in a range of different hosts. In addition, the C-terminal PDZ-binding motif (PBM) has been suggested as a pathogenic determinant of IAVs. To gauge the pandemic potential from human and avian IAV reassortment, we assessed the replication properties of NS-reassorted viruses in cultured cells and in the lungs of mice and determined their transmissibility in guinea pigs. Compared with the recombinant A/Korea/01/2009 virus (rK09; 2009 pandemic H1N1 strain), the rK09/VN:NS virus, in which the NS gene was adopted from the A/Vietnam/1203/2004 virus (a human isolate of the highly pathogenic avian influenza H5N1 virus strains), exhibited attenuated virulence and reduced transmissibility. However, the rK09/VN:NS-PBM virus, harboring the PBM in the C-terminus of the NS1 protein, recovered the attenuated virulence of the rK09/VN:NS virus. In a guinea pig model, the rK09/VN:NS-PBM virus showed even greater transmission efficiency than the rK/09 virus. These results suggest that the PBM in the NS1 protein may determine viral persistence in the human and avian IAV interface.
Copyright ? 2014. Published by Elsevier Inc.
KEYWORDS:
Influenza A virus, Interferon, NS1 protein, PDZ-binding motif, Transmission
PMID:
24802398
[PubMed - as supplied by publisher]
